Phosgenation under pressure of alcohol&#39;s for producing chloroformates

ABSTRACT

The invention concerns a method for phosgenation of monohydroxy alcohol&#39;s and/or polyols characterised in that it consists of treating alcohol and or polyol, whether in the presence of solvent or not, with a molar excess of phosgene, preferably 2 to 30 times more phosgene than the hydroxyl groups, at temperatures ranging between 0 and 200° C. and at pressure levels ranging between 2 and 60 bar, preferably in the absence of any catalyst. The method is further characterised in that pressure is further used to facilitate the separation of hydrochloric acid from phosgene, in a column external to the reactor.

The present invention relates to a new process for obtainingchloroformates by phosgenating the corresponding alcohols under pressurewith or without a catalyst, preferably in the absence of a catalyst.

Conventional processes consist in injecting phosgene into the alcohol,alone or in solution, under atmospheric pressure. In general, an excessof phosgene is used. The educts, consisting of a mixture of phosgene andhydrochloric acid, are inseparable under atmospheric pressure unlessvery low temperature condensers are used, which always results in a lossof phosgene.

The chemistry is governed by the following equation:

R(OH)_(n)+nCOCl₂ →R (OCOCl)_(n) +nHCl   (k)

In order to activate the reaction, it is necessary to employ one or morecatalysts; consequently, there is numerous literature concerning thesederivatives. The use of a catalyst, however, presents a number ofdisadvantages. Foremost among these is their cost, followed by theirinfluence on the choice of materials, since the catalysts often make thereaction system highly corrosive. Further, the catalyst promotes theformation of by-products and the development of discoloration. Finally,it necessitates purification of the chloroformate by distillation orcrystallization.

The aim of the invention is to avoid the abovementioned disadvantagesthat are associated, in particular, with the use of catalysts.

The invention provides a process for phosgenating monohydroxy alcoholsand/or polyols to obtain the corresponding chloroformates, characterizedin that the alcohol and/or polyol are/is treated in the presence orabsence of solvent with a molar excess of phosgene, preferably fromapproximately 2 to 30 times more phosgene per hydroxyl group, at atemperature of between 0 and 200° C. and at a pressure of between 2 and60 bar (1 bar =10⁵ Pa) with or without a catalyst, preferably in theabsence of any catalyst. The process is generally carried out in aclosed system (autogenous pressure) or in an open system (pressureregulated by partial degassing, for example). The process is generallyoperated continuously or semicontinuously. It is preferred to operate inan open system with partial degassing. Degassing must be carried outwhile ensuring that an excess of phosgene remains. This is done eitherby selective removal of the hydrochloric acid, while retaining theexcess of phosgene and a little HCl, or by a degassing which includesthe phosgene, with the latter being resupplied at the same time. Thetemperature is advantageously selected between 20 and 150° C.,preferably between 25 and 80° C., while the pressure is selectedpreferably between 6 and 40 bar. The temperature and pressure conditionsare determined by the nature of the alcohol and/or polyol and of thecorresponding chloroformate, in particular by the critical point and/ordecomposition point.

The advantages of the pressure phosgenation according to the inventionare to be able a) to make it possible to do away with the lowtemperature condensers, b) to do away with solvent and/or catalyst, andc) to obtain chloroformates with little or no by-products such ascarbonates and chlorides. This makes it possible to avoid finalpurification of the resulting chloroformate, to have a simple separationat the end of the reaction, and to reduce the cost of utilities, theadvantages, in general terms, being those already discussed above andlinked with the absence of catalyst.

The process according to the invention is advantageously employed forconverting alcohols and/or polyols of formula R(OH)_(n) tochloroformates R(OCOCl)_(n), n being an integer from 1 to 6 and R beingdefined as follows:

- a saturated or unsaturated, linear or branched aliphatic radicalhaving 1 to 22 carbon atoms which is optionally substituted a) by one ormore identical or different halogen atoms, b) by one or more nitrogroups, or c) by at least one alkyloxy, aryl (preferably phenyl),aryloxy or arylthio group, each of these groups being unsubstituted orsubstituted;

- a saturated or unsaturated, linear or branched polyoxyalkylene radicalwhich is optionally substituted by the substituents indicated above andhas a molecular mass of between 200 and 6000 (with the proviso that thealcohols are liquid or can be dissolved under the reaction conditions);

- a cycloaliphatic radical having 3 to 8 carbon atoms which bears ordoes not bear one or more substituents selected from a) halogen atoms,b) alkyl or haloalkyl radicals, c) nitro groups and d) aryl (preferablyphenyl), aryloxy or arylthio radicals, it being possible for theseradicals themselves to be unsubstituted or substituted;

- an aromatic carbocyclic radical which is unsubstituted or substitutedby one or more substituents selected from the group consisting ofhalogen atoms, alkyl or haloalkyl radicals (preferably CF₃) having 1 to12 carbon atoms (for example C₂-C₆ alkenyl, C₃-C₈ cycloalkyl, C₄-C₁₀cycloalkylalkyl, C₇-C₁₀ aralkyl and C₇-C₁₀ aralkoxy), alkylthio orhaloalkylthio radicals having 1 to 6 carbon atoms, alkylsulphinyl orhaloalkylsulphinyl radicals having 1 to 6 carbon atoms, alkylsulphonylor haloalkylsulphonyl radicals having 1 to 6 carbon atoms, alkyloxy orhaloalkyloxy radicals having 1 to 6 carbon atoms, aryl, arylthio oraryloxy radicals, and the nitro group;

- a 5- or 6-membered aromatic or nonaromatic heterocyclic radical havingone or more identical or different heteroatoms selected from oxygen,sulphur and nitrogen atoms and being unsubstituted or substituted by oneor more substituents selected from halogen atoms, nitro groups, alkyl,haloalkyl, alkyloxy, haloalkyloxy, aryl, arylthio and aryloxy radicalsand/or being optionally condensed with an aromatic carbocycle whichitself is unsubstituted or substituted.

In general, when an aryl group (or one of its derivatives such asaryloxy or arylthio) or an aromatic carbocycle is mentioned, it shouldbe considered, even if not stated at the time when such a radicalappears, in order to lighten the present specification, that the saidgroup or carbocycle can bear substituents selected from the groupconsisting of halogen atoms and alkyl, haloalkyl, alkyloxy,haloalkyloxy, alkylthio, haloalkylthio, alkylsulphinyl,haloalkylsulphinyl, alkylsulphonyl, haloalkylsulphonyl, aryl, aryloxy,arylthio and nitro radicals.

The process according to the invention is also suitable for convertingmixtures of monohydroxy alcohols and/or mixtures of monohydroxy alcoholsand polyols to corresponding chloroformates.

This process according to the invention is likewise characterized inthat the pressure is further used to facilitate the separation of thehydrochloric acid and the phosgene in a column external to the reactor,without employing low temperature condensers which are, as has alreadybeen seen, a source of COCl₂ losses. The separation hence becomes moresimple, and thus more economic, than with the known processes, and leadsto readily recyclable phosgene and to pure hydrochloric acid.

The examples which follow are given purely by way of illustration of theinvention, which they do not limit in any way whatsoever.

Process for preparing chloroformates by pressure phosgenation ofmonohydroxy alcohols

These examples demonstrate the advantages linked to the processaccording to the invention, which was monitored by a two-dimensionalfield gradient NMR method. Kinetic monitoring was also carried out.

The NMR analyses under pressure were carried out on an AMX 300spectrometer operating at 300 MHz for the proton and equipped with a 5mm z-gradient QNP ¹H/¹³C/¹⁹F/³¹P probe. The chemical shifts (δ) of theproton and carbon resonance signals are expressed in ppm relative todeuterated DMSO (39.5 ppm in ¹³C NMR and 2.24 ppm in ¹H NMR). For thisexample and for the following examples, the monocrystalline sapphiretube has internal and external diameters of 4 and 5 mm respectively.

The alcohol is introduced into this tube along with a capillarycontaining deuterated DMSO, in order to ensure field/frequency lock. Thetitanium head is fitted onto the tube, which is then immersed in adry-ice/acetone bath (−78° C.) so as to condense the phosgene (which isintroduced via a valve situated atop the head of the tube). The mediumis allowed to return to ambient temperature (approximately 15 minutes)before the NMR measurements are conducted.

EXAMPLE 1 Phosgenation of benzyl alcohol

In accordance with the general procedure described above, 98.4 mg (0.89mmol) of alcohol and 302.3 mg (3.05 mmol) of phosgene are introducedinto the tube, corresponding to a phosgene/alcohol molar ratio of 3.4.The phosgene serves additionally as solvent.

Besides phosgene, the following three compounds were characterized:alcohol, chloroformate and benzyl chloride.

On the other hand, no benzyl carbonate was formed. It is therefore seenthat, in addition to the fact that the chloroformate is produced undergood conditions, the two other advantages of this process reside in thepossibility of preventing or limiting the production of carbonate andchloride.

The NMR peaks of the CH₂ protons of the three abovementioned productsare readily separated and identified. The intensity of thesecharacteristic signals is monitored over time. The study is conducted at300 K, and from the very first spectra it is noted that the degree ofconversion of the benzyl alcohol is high: greater than 90% (cf. tablebelow). The results show that the chloroformate forms rapidly andpredominantly.

Molar proportions, % Time (min) Benzyl alcohol Chloroformate Benzylchloride  0* 7 92 1  5 6 93 1 17 3 95 2 53 1 96 3 80 <1 97 3 *this timet = 0 corresponds to the end of recording of the 1st proton spectrum

EXAMPLE 2 Phosgenation of isopropanol

In accordance with the general procedure described above, 66.2 mg (1.09mmol) of alcohol and 186.0 mg (1.88 mmol) of phosgene are introducedinto the tube, corresponding to a phosgene/alcohol molar ratio of 1.7.The phosgene serves additionally as solvent.

Besides phosgene, the following three compounds characterized: alcohol,chloroformate and isopropyl chloride.

The NMR sextuplets of the CH protons of the three abovementionedproducts are readily separated and identified. The intensity of thesecharacteristic signals is monitored over time. The study is conducted at300 K, and from the very first spectra it is noted that the degree ofconversion of the isopropanol is high: greater than 70% (cf. tablebelow). The results show that the chloroformate forms rapidly andpredominantly.

Molar proportions, % Time (min) Isopropanol Chloroformate Isopropylchloride  0* 33.0 67.0 —  18 29.4 70.6 —  39 24.8 73.9 1.3  50 24.0 74.51.5  82 19.3 78.4 2.3 113 17.7 79.1 3.2 162 13.7 82.3 4.0 232 11.3 82.16.6 * this time t = 0 corresponds to the end of recording of the 1stproton spectrum

Plotting the negative natural logarithm of the quantity 1-DC (where DC=degree of conversion =(100 molar % of isopropanol)/100) as a functionof time gives a straight line (cf. FIG. 1). The apparent order of thereaction of formation of chloroformate from isopropanol is therefore 1.The slope of this straight line is equal to the rate constant of thereaction: k =0.3 h⁻¹. The half-life time t_(1/2), which represents thetime required for the isopropanol concentration to reduce by half, isequal to 1n2/k (t_(1/2)=approximately 2 h 15 min).

Process for preparing chloroformates by pressure phosgenation of diols

The NMR analyses under pressure were carried out on an AMX 300spectrometer operating at 300 MHz for the proton and equipped with a 5mm z-gradient QNP ¹H/¹³C/¹⁹F/^(3l)P probe. The chemical shifts (δ) ofthe proton and carbon resonance signals are expressed in ppm relativeto-deuterated DMSO (39.5 ppm in¹³C NMR and 2.24 ppm in ¹H NMR). For thisexample and for the following examples, the monocrystalline sapphiretube has internal and external diameters of 4 and 5 mm respectively.

The polyol is introduced into this tube along with a capillarycontaining deuterated DMSO, in order to ensure field/frequency lock. Thetitanium head is fitted onto the tube, which is then immersed in adry-ice/acetone bath (−78° C.) so as to condense the phosgene (which isintroduced via a valve situated atop the head of the tube). The mediumis allowed to return to ambient temperature (approximately 15 minutes)before the NMR measurements are conducted.

EXAMPLE 3 Phosgenation of ethylene glycol under pressure

In accordance with the general procedure described above, 105.1 mg (1.69mmol) of ethylene glycol and 1006 mg (10.2 mmol) of phosgene areintroduced into the tube, corresponding to a phosgene/glycol molar ratioof 6. The phosgene serves additionally as solvent.

The reaction at 300 K is monitored by proton NMR and the phosgenationproducts are identified by one- and two-dimensional carbon and protonNMR.

After approximately 20 minutes of reaction at 300 K (between the end ofpreparation of the tube and the first proton NMR analysis), 62 molar %of dichloroformate (1), 14 molar % of carbonate (2) and 23 molar % ofproduct (3) =ClCOO(CH₂)₂Cl are observed. No ethylene glycol is observed.The structure of the products formed is confirmed by gaschromatography/infrared/mass spectrometry analysis.

The results show that the dichloroformate is formed rapidly andpredominantly.

Molar proportions, % Time (min) (1) (2) (3) 20 62 14 23 38 66 18 16 10070 20 9 163 71 23 5 355 70 27 2

EXAMPLE 4 Phosgenation of a polyethylene glycol (PEG) under pressure

In accordance with the general procedure described above, 113.8 mg (0.28mmol) of polyethylene glycol and 576.6 mg (5.82 mmol) of phosgene areintroduced into the tube, corresponding to a phosgene/PEG molar ratio of20.8. The phosgene serves additionally as solvent.

The polyethylene glycol (PEG) chosen has a mass of approximately 400 M.

After approximately 20 minutes of reaction at 300 K (between the end ofpreparation of the tube and the first proton NMR analysis), 4 multipletsare observed:

- 1 peak at 3.59 ppm corresponding to the “central” OCH₂ protons of thePEG

- 1 multiplet at 3.71 ppm, with an intensity of 2

- 1 multiplet at 4.39 ppm, with an intensity of 2

- 1 broad multiplet at approximately 4.8, with an intensity of 1

This spectrum does not change at 300 K over 3 hours. Subsequently, weheated the system at 373 K for approximately 1 hour; we still obtainedthe same spectrum.

This allows us to consider that we have:

- either the product (4) where R′ is probably OH, although R′=Cl cannotbe excluded.

- or an equimolar mixture of PEG and “dichloroformate”.

The first hypothesis appears the most likely. The structure of theproducts formed cannot be confirmed by gas chromatography/infrared/massspectrometry analysis, since the mass of the compounds is too high.

Process for preparing chloroformates by pressure phosgenation ofaromatic alcohols

The NMR analyses under pressure were carried out on an AMX 300spectrometer operating at 300 MHz for the proton and equipped with a 5mm z-gradient QNP ¹H/¹³C/¹⁹F/³¹P probe. The chemical shifts (δ) of theproton and carbon resonance signals are expressed in ppm relative todeuterated DMSO (39.5 ppm in ¹³C NMR and 2.24 ppm in ¹H NMR). For thisexample and for the following examples, the monocrystalline sapphiretube has internal and external diameters of 4and 5 mm respectively.

The alcohol is introduced into this tube along with a capillarycontaining deuterated DMSO, in order to ensure field/frequency lock. Thetitanium head is fitted onto the tube, which is then immersed in adry-ice/acetone bath (−78° C.) so as to condense the phosgene (which isintroduced via a valve situated atop the head of the tube). The mediumis allowed to return to ambient temperature (approximately 15 minutes)before the NMR measurements are conducted.

EXAMPLE 5 Phosgenation of phenol under pressure

In accordance with the general procedure described above, 43 mg (0.45mmol) of phenol and 783 mg (7.9 mmol) of phosgene were introduced intothe tube, corresponding to a phosgene/phenol molar ratio of 18. Thephosgene serves additionally as solvent.

The sapphire tube was heated for approximately 10 h at 403 K (130° C.)and then for 7 h at 413 K (140° C.) in a silicone oil bath.

After heating at 413 K, in the proton and the carbon NMR, we observe theappearance of peaks of low intensity which are compatible with thepresence of phenyl chloroformate (the chemical shifts of the proton andcarbon 13 resonance peaks are indicated below for a product whose molarpurity is estimated to be greater than 98%)

EXAMPLE 6 Phosgenation of 2-naphthol under pressure

In accordance with the general procedure described above, 31 mg (0.21mmol) of 2-naphthol, 537 mg (5.4 mmol) of phosgene, corresponding to aphosgene/naphthol molar ratio of 26, and 688 mg (6.1 mmol) ofchlorobenzene are introduced into the tube.

The 2-naphthol introduced is completely soluble in the chlorobenzene at300 K. At 300 K, no reaction of the 2-naphthol is observed. At 393 K,after 5 h, the appearance of NMR signals of low intensity is observed,which we did not identify but which are compatible with the presence of2-naphthyl chloroformate.

Process for preparing chloroformates by pressure phosgenation in a 2litre autoclave EXAMPLE 7 Preparation of n-octyl chloroformate

In a 2 litre autoclave, which is dried previously and is equipped with acondenser fed with glycolated water at −15° C. and equipped with apressure regulation system, 890 g of monochlorobenzene are introducedand then 594 g (6 mol) of liquid phosgene are added, during which thereactor is cooled. This is followed by the rapid introduction of 130 g(1 mol) of n-octanol, and the air connection valve is closed. Thereaction medium is heated to 50° C. The relative pressure reached is 3.2bar. Argon is added to give a relative pressure of 11.5 bar, and thenthe reaction mixture is held at 50° C. for 1 hour. Pressure regulationat 11.2 bar (relative) takes place without further addition of argon.The reaction medium is subsequently cooled to approximately 20° C. anddecompressed.

Analysis of the reaction medium by ¹H NMR shows that n-octylchloroformate has formed and there is no residual alcohol, no ether andno carbonate. Analysis by gas chromatography indicates a 1-chlorooctanecontent of 0.3 molar %, giving an estimated purity of the n-octylchloroformate of 99.7%.

EXAMPLE 8 Preparation of the chloroformate of a heavy alcohol

In the present example, the alcohol phosgenated is polyoxybutylenealcohol 1616 (POBA) from the company Dow Chemical, having an averagemolar mass of 1400 and the following formula:

In the 2 litre autoclave, which is equipped and dried as in Example 7,the monochlorobenzene (500 g) is charged and 141 g of phosgene (1.42mol) are introduced, during which the reaction medium is cooled withwater. Subsequently, via a pump, 200 g of polyoxybutylene alcohol (0.143mol) in solution in 400 g of monochlorobenzene are introduced and theair connection is closed. The reaction medium is heated to 60° C. Therelative pressure reaches 10 bar. The relative pressure is then raisedto 11.5 bar by adding argon under pressure. These conditions aremaintained for 4 hours. The regulation of relative pressure takes placeto 11.2 bar. The system is cooled to ambient temperature, at which pointthe relative pressure is 8.8 bar, and the reaction medium isdecompressed. 1214 g are obtained, for a theoretical mass of 1232.1 g.

NMR monitoring is not possible. The yield of the synthesis is determinedby assaying the proportion of phosgene and the proportion ofhydrolysable chlorine on an aliquot of reaction medium.

After degassing and concentration, the proportion of hydrolysablechlorine is 3.58% and the proportion of phosgene is 4.46%, correspondingto 0.126 mol of chloroformate.

The yield in terms of chioroformate of the polyoxybutylene alcohol is88%.

Infrared identification: presence of the CO band at 1781 cm⁻¹.

The colour of the resulting product is comparable to that of thestarting alcohol.

EXAMPLE 9 Preparation of 2-perfluorohexylethyl chloroformate

In the 2 litre autoclave, treated and equipped as before, 600 ml ofmonochlorobenzene and 85 g of phosgene are introduced, during which thereactor is cooled.

The reactor is closed and cooled to 0° C., and 50 g of2-perfluorohexylethanol are introduced under subatmospheric pressure.Nitrogen is added to give an absolute pressure of 12 bar and then thereaction medium is heated at 75° C. for 2 hours during which pressureregulation is maintained.

The reactor is subsequently decompressed and the reaction medium isdistilled under reduced pressure in order to remove themonochlorobenzene. 30.5 g of concentrate are collected, containing amixture of 80 g of 2-perfluorohexylethyl chloroformate and 20 g ofdi-2-perfluorohexylethyl carbonate.

What is claimed is:
 1. Process for phosgenating monohydroxy alcoholsand/or polyols to obtain the corresponding chloroformates, whichcomprises reacting the alcohol and/or polyol in the presence or absenceof solvent with a molar amount of phosgene of at least 3.4 per hydroxylgroup, at a temperatures of between 0 and 200° C. and at a pressure ofbetween 2 and 60 bar without a catalyst.
 2. Process according to claim 1wherein the reaction is carried out with up to 30 times more phosgenerelative to each hydroxyl group.
 3. Process according to claim 1 or 2,wherein the reaction is carried out in an open system with partialdegassing.
 4. Process according to claim 1 or 2 wherein the reactiontemperature is between 20 and 150° C.
 5. Process according to claim 1wherein the pressure is between 6 and 40 bar.
 6. Process according toclaim 1 wherein an alcohol and/or polyol of formula R(OH)_(n) isconverted to a chloroformate R(OCOCl)_(n), n being an integer from 1 to6 and R being defined as follows: - a saturated or unsaturated, linearor branched aliphatic radical having 1 to 22 carbon atoms which isoptionally substituted a) by one or more identical or different halogenatoms, b) by one or more nitro groups, or c) by at least one alkyloxy,aryl, aryloxy or arylthio group, each of these groups beingunsubstituted or substituted; - a saturated or unsaturated, linear orbranched polyoxyalkylene radical which is optionally substituted by thesubstituents indicated above and has a molecular mass of between 200 and6000 (with the proviso that the alcohols are liquid or can be dissolvedunder the reaction conditions); - a cycloaliphatic radical having 3 to 8carbon atoms which bears or does not bear one or more substituentsselected from a) halogen atoms, b) alkyl or haloalkyl radicals, c) nitrogroups and d) aryl, aryloxy or arylthio radicals, it being possible forthese radicals themselves to be unsubstituted or substituted; - anaromatic carbocylic radical which is unsubstituted or substituted by oneor ore substituents selected from the group consisting of halogen atoms,alkyl or haloalkyl radicals having 1 to 12 carbon atoms, C₂-C₆ alkenyl,C₃-C₈ cycloalkyl, C₄-C₁₀ cycloalkylalkyl, C₇-C₁₀ aralkyl and C₇-C₁₀aralkoxy radicals, alkylthio or haloalkylthio radicals having 1 to 6carbon atoms, alkylsulphinyl or haloalkylsulphinyl radicals having 1 to6 carbon atoms, alkylsulphonyl or haloalkylsulphonyl radicals having 1to 6 carbon atoms, alkyloxy or haloalkyloxy radicals having 1 to 6carbon atoms, aryl, arylthio or aryloxy radicals, and the nitro group; -a 5- or 6-membered aromatic or nonaromatic heterocyclic radical havingone or more identical or different heretoatoms selected from oxygen,sulphur and nitrogen atoms and being unsubstituted or substituted by oneor more substituents selected from halogen atoms, nitro groups, alkyl,haloalkyl, alkyloxy, haloalkyloxy, aryl, arylthio and aryloxy radicalsand/or being optionally condensed with an aromatic carbocycle whichitself is unsubstituted or substituted.
 7. Process according to claim 1or 2 wherein a mixture of monohydroxy alcohols is converted tochloroformates.
 8. Process according to claim 1 or 2 wherein a mixtureof monohydroxy alcohols and polyols is converted to chloroformates.